Improvements in cancer diagnostics and therapeutics have positively impacted outcomes for oncology patients within select clinical niches. However, significant therapeutic uncertainty awaits the majority of today's oncology patients who present in the clinic with cancer that will relapse after exhibiting an initial response or whose cancer is already refractory to standard of care (SOC) therapy. Unfortunately, the absence of technology that accurately predicts a patient's non-response to SOC means many patients will experience toxic side effects to systemic therapy without receiving clinical benefit. Such patients will also lose valuable time and money that could be used to identify and finance more effective treatments and, in some cases under the selective pressure induced by suboptimal therapy, will develop pan resistance rendering alternate treatments ineffective. Successful translation of Presage's innovative CIVO technology into the oncology clinic will provide a personalized system that identifies patients whose cancer is not going to respond to SOC; thereby limiting unwarranted exposure to costly, ineffective therapy and its associated toxicity while increasing time available for evaluation of new therapeutic modalities at earlier stages of disease. Specifically, CIVO is a hand-held microinjection device engineered to deliver minute amounts of up to eight drugs or drug combinations directly into a patient's solid tumor. CIVO is complemented by an automated analytical package that measures tumor cell specific and microenvironment alterations at the single cell level, revealing comprehensive profiles of an individual's tumor response to each injected agent. Furthermore, CIVO is superior to alternative platforms developed to predict tumor response to chemotherapy due to CIVO's enablement of evaluating drug response in vivo, in the patients living tumor, in the natural context of native tumor stroma and the host immune system. The CIVO clinical trial detailed in this application is designed to establish the negative predictive value (NPV) of CIVO in diffuse large B cell lymphoma (DLBCL) patients who are candidates for one of three second line SOC therapies. The initial training stage of the trial will be a non- blinded, retrospective study used to establih CIVO quantitative thresholds for determining if a patient's lymphoma is non-responsive to microinjected drug in relation to the patient's response to systemic therapy. The second stage, or Test phase, of the trial will employ the quantitative threshold(s) obtained from the training stage to determine if CIVO can predict non-response to systemic second line therapy. SBIR support in establishing CIVO clinical NPV in DLBCL will build the clinical foundation required to expand translation of CIVO into additional tumor types, serving to drive more efficient and cost effective patient segregation and therapeutic selection in the oncology clinic.